Studies from our group and others indicate that non-adherence to hydroxyurea (HU) therapy and clinic visits is high and problematic, limiting the potential for these therapies to improve physical and psychosocial health in patients. Despite the documented importance of adherence, there is a dearth of evidence-based practices for identifying and resolving barriers to HU therapy and clinic attendance in SCO. Intervention approaches within the context of a patient's routine clinic visit and provider-patient communication are especially limited. The primary aims of the proposed innovative study are: (1) to refine a computerized and voice-automated version of a tool that was developed in our preliminary studies to identify barriers and facilitators to adherence to HU and clinic attendance among patients and parents; (2) to implement an intervention program (based on Behavior Family Systems Therapy; BFST) that reduces barriers and increases facilitators to adherence via providerpatient problem-solving, disease management plans, memory aids, phone support and follow-up, etc. BFST and other intervention approaches have been shown efficacious in promoting adherence in other pediatric chronic illness groups (e.g., asthma, cystic fibrosis, diabetes). The secondary aims of this study are to improve adherence, quality of life, and health outcomes in patients over the 12- month intervention period and to maintain benefits during the follow-up phase of the project. Sixty (n=60) patients on HU, ages 6 to 21 and parents of patients ages 6 to 17, will complete the intervention with trained nurses and social workers during standard of care outpatient clinic visits over 12 months. Patient-report assessments of adherence and barriers, quality of life, health outcomes, and clinic satisfaction will be completed at baseline, 3, 6, 9 and 12 months (postintervention) and at 18 and 24 months (follow-up period). Clinical adherence measures (changes in fetal hemoglobin and neutrophil count) and clinic attendance will be monitored via through the patient's electronic medical record throughout the intervention and follow-up period. As a long range goal, we will work to generalize such adherence intervention programs and strategies to other centers, treatments and patients, ultimately improving quality of life and reducing morbidity and mortality in patients with SCD.